Disease-specific alterations in the expression of circulating extracellular vesicle surface proteins in sepsis, hypertension and hypertensive sepsis.

The diagnostic approach for sepsis is complicated by its pathophysiological heterogeneity and the absence of a gold-standard test. Moreover, the high prevalence of preexisting chronic diseases, specifically hypertension, further complicates clinical interpretation. Recently, extracellular vesicles (EVs) have emerged as a rich source of diagnostic biomarkers for several diseases, including sepsis and hypertension, because of their critical role in intercellular communication and inflammation. Therefore, this study aimed to explore the effects of sepsis, hypertension, and their comorbidities on the surface protein markers of small EVs (sEVs), offering a novel avenue for diagnostic discovery. sEVs were isolated from different groups (healthy controls, hypertensive, septic, and hypertensive-septic patients; n = 12 per group) and fully characterized, and their surface markers were identified via the MACSPlex exosome kit (a flow cytometry-based technique). Distinct profiles were identified across the hypertension, sepsis, and hypertensive-sepsis groups, revealing differentially expressed surface markers compared with healthy controls or between disease states. Our findings reveal preliminary disease-specific surface signatures under MACSPlex detection. The identification of these unique biosignatures provides a foundational framework for pioneering sEV-based diagnostic strategies. This work holds significant promise for improving patient stratification, enabling more precise biomarker-driven insights into the complex interplay of sepsis and hypertension.